Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 2 of 31 Lithium Hypochlorite Registration Review Team

Human Health Jonathan Leshin Timothy Dole

Environmental Fate and Effects William Erickson Srinivas Gowda Najm Shamim

Risk Management Donna Kamarei Rose Kyprianou Wanda Henson

Office of General Counsel Philip RossDocket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 3 of 31 

### Table of Contents
1 Introduction .................................................................................................................. ........ 5 1.1 Statutory and Regulatory Authority .............................................................................. 5 1.2 Case Overview ............................................................................................................... 6 1.3 Chemical Identification and Properties ......................................................................... 7 1.4 Use/Usage Description .................................................................................................. 8 1.4.1 Summary of Regist ered Uses ................................................................................. 8 1.5 Regulatory History ........................................................................................................ 9 1.5.1 Recent/Pending Regulatory Actions ...................................................................... 9 1.5.2 Tolerance Information ............................................................................................ 9 1.6 Incidents ..................................................................................................................... .... 9 1.6.1 Human Health ........................................................................................................ 9 1.6.2 Ecological ............................................................................................................... 9 2 Anticipated Data Needs ........................................................................................................ 9 3 Human Health Risk Assessment ........................................................................................ 10 3.1 Existing Toxicological Endpoints ............................................................................... 10 3.2 Dietary Exposure .......................................................................................................... .... 11 3.3 Occupational and Resi dential Exposures ......................................................................... 11 3.4 Aggregate and Cumulative Exposure ............................................................................... 11 4 Environmental Risk Assessment ........................................................................................ 11 4.1 Environmental Fate and Exposure Pathways .............................................................. 11 4.1.1 Water Quality ....................................................................................................... 12 4.2 Ecological Effects Assessment .................................................................................... 12 4.2.1 Mode of Action .................................................................................................... 12 4.2.2 Measures of Effect (Ecotoxicology Assessment Endpoints) ............................... 12 4.3 Exposure Analysis Plan ............................................................................................... 14 4.3.1 Aquatic and Terrestrial Wild life Exposure Estimates .......................................... 14 5 Endocrine Disruptor Screen ing Program (EDSP) .............................................................. 14 6 Optional Label Changes ..................................................................................................... 15 7 Guidance for Commenters ................................................................................................. 15 7.1 Preliminary Work Plan ................................................................................................ 15 7.1.1 Trade Irritants ....................................................................................................... 16 7.1.2 Water Quality ....................................................................................................... 16 7.1.3 Environmental Justice .......................................................................................... 16 7.1.4 Structure Activity Relationships .......................................................................... 16 7.1.5 Additional Information ......................................................................................... 17 8 Next Steps .................................................................................................................... ...... 18 9 References .................................................................................................................... ...... 19Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 4 of 31 Appendix A Toxicology Profile ...................................................................................................... 22 Appendix B Environmental Fate and Transpor t of Lithium Hypochlorite ..................................... 24 Appendix C Ecotoxicology Profile ................................................................................................. 27 Appendix D Product Chemistry ...................................................................................................... 30

List of Tables Table 1 – Summary of Anticipated Risk Assessments and Data Needs: Lithium Hypochlorite ...... 6 Table 2 – Anticipated Registration Review Schedule for Lithium Hypochlorite ............................. 6 Table 3 – Chemical Identification of Lithium Hypochlorite ............................................................. 7 Table 4 – Physical-Chemical a nd Environmental Fate Propertie s for Lithium Hypochlorite .......... 7 Table 5 – Summary of Lithium Hypochlorite Registered Uses ........................................................ 8 Table 6 – Available Ecological Effects Endpoint s for the Ecological Assessment of Lithium Hypochlorite....................................................................................................13 Table 7 – Acute Toxicity Data for Lithium Hypochlorite..............................................................22

List of Figures None.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 5 of 31 

## 1 Introduction

This document is the Environmen tal Protection Agency’s (EPA or “the agency”) Preliminary Work Plan (PWP) for lithium hypochlorite. The PWP document explains what EPA's Office of Pesticide Programs knows about lithium hypochl orite, highlighting anticipated data and assessment needs, identifying the types of inform ation that would be espe cially useful to the agency in conducting the review, and providing an anticipated timeline for completing lithium hypochlorite’s review.

The registration review process wa s designed to include a public par ticipation component to solicit input from interested stakeholders . The agency intends, by sharing this information in the docket, to inform the public of what it knows about lith ium hypochlorite and what types of new data or other information would be help ful for the agency to receive as it moves toward a decision on lithium hypochlorite. The agency encourages all inte rested stakeholders to review the PWP and to provide comments and additional information that will help the agency’s decision-making process for this chemical.



## 1.1 Statutory and Regu latory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the U.S. Environmental Protection Agency based on scien tific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all register ed pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practi ces will occur over time. Through the registration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safel y. Information on this program is provided at http://www.epa.gov/oppsrrd1/ registration_review/.

The agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The agency will consider benefits information and data as re quired by FIFRA. The public phase of registration review begins when the initial docket is ope ned for each case. The docket is the agency’s opportunity to state what it knows ab out the pesticide and what addi tional risk analyses and data or information it believes are need ed to make a registration revi ew decision. After reviewing and responding to comments and data received in th e docket during this init ial comment period, the agency will develop and commit to a Final Work Plan (FWP) and antici pated schedule for the lithium hypochlorite case. The agency may combine this case with sodium and calcium hypochlorite (case 0029).

Documents associated with this registration re view can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP-2013-0606. Tables 1 and 2 belo w summarize the issues relevant to this registration review case and the anticipated regist ration review schedule.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 6 of 31 Table 1 – Summary of Anticipate d Risk Assessments and Data Needs: Lithium Hypochlorite

Risk Assessment Assessment Necessary to Support Registration Review Date of Most Recent Assessment Type of Assessment Required (New/Updated) Data Anticipated as Needed

Dietary (food) No (see section 3.2) None None None
Dietary (drinking water) No (see section 3.2) None None None
Occupational Handler No (see section 3.3) None None None

Residential Handler No (see section 3.3) None None None
Aggregate No (see section 3.4) None None None

Cumulative No (see section 3.4) None None None

Tolerance Review No (see section 1.5.2) None None None

Ecological Yes December 1 st , 1993 New (swimming pools) None

Table 2 – Anticipated Registration Revi ew Schedule for Lithium Hypochlorite
Anticipated Activity Target Date* Completion Date Phase 1: Openin g the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2014-03 March 26, 2014 Close Public Comment Period 2014-05 Phase 2: Case Development Issue Final Work Plan 2014-09 Issue Data Call-In (DCI) N/A Receive Data to be Considered in Risk Assessment N/A Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2016-03 Close Public Comment Period 2016-04 Phase 3: Registration Review Decision and Implementation Open 60-Day Public Comment Period for Proposed Decision 2016-09 Close Public Comment Period 2016-11 Issue Final Decision 2017-03 Begin Post-Decision Followup 2017 Total (years) 3 *The anticipated schedule will be revised as necessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).



## 1.2 Case Overview
The docket for the lithium hypochlorite case (case 3084) has been established at http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0606.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 7 of 31 

## 1.3 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in case 3084: lithium hypochlorite (PC Code 014702).

Table 3 – Chemical Identificati on of Lithium Hypochlorite

Chemical Name Lithium Hypochlorite Chemical Classification Halogen
PC Code 014702
CAS Number 13840-33-0 Molecular Formula LiOCl Molecular Weight (grams/mole) 58.4 Purity 29% LiOCl Available chlorine 35%

Molecular Structure

The lithium hypochlorite product chemistry information relevant to risk assessment is summarized in Table 4 (source: MRIDs 7257, 7258, 94669, 93138001, 42940801, 42967001, 42967002, 42967003, 42991801, 31007-02, 31007-03, 5045001-15).

Table 4 – Physical-Chemical and Environmental Fate Properties for Lithium Hypochlorite

Guideline No. Parameter Lithium Hypochlorite (29%)
Physical/Chemical Properties

830.7000 pH 9.9 (available Cl 2 - 100 ppm) in dist. water at 25°C. 10.3 (available Cl 2 - 200 ppm) in dist. water at 25°C. 10.7 (available Cl 2 - 300 ppm) in dist. water at 25°C.

11 at 25 °C (1% Solution) 830.7050 UV/Visible Absorption Not reported 830.7200 Melting point 135°C with decomposition 830.7220 Boiling point ( o C) Not applicable
830.7300 Density 0.531 g/cm 3 (20 °C) Bulk Density: 58 lbs/ft 3 830.7370 Dissociation constant (pKa) 3.2 x 10 -8 (of HOCl in aqueous solution)

830.7550 Octanol-water partition coefficient at 25 o C (Log K ow ) Not applicable
830.7840 Solubility in water (mg/L) 43% by weight at 25°C 830.7950 Vapor pressure (mmHg) 6.63 x 10 -17 mm Hg (EPI Suite v 4.1) Environmental Fate Properties
Henry's law constant at 25 o C (atm-m 3 /mol) Not applicable; very low vapor pressure ; inorganic substance Octanol-air partition coefficient at 25 o C (Log K OA ) Not applicableDocket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 8 of 31 Guideline No. Parameter Lithium Hypochlorite (29%)
Air-water partition coefficient (Log K A W ) Not applicable Mobility Organic Carbon Partitioning Coefficient (K oc ) Persistence in Water (half-life) Hydrolysis at 25 o C: pH 5, 7 & 9 (days) Not applicable; inorganic substance Aqueous photolysis at 25 o C (days) Not applicable; inorganic substance Aerobic aquatic metabolism (days) Not applicable; inorganic substance Anaerobic aquatic metabolism half-life (days) Not applicable; inorganic substance Persistence in Soil (half-lifes) Soil photolysis (days) Not applicable; inorganic substance Aerobic soil metabolism at 25 o C (days) Not applicable; inorganic substance Anaerobic soil metabolism (days) Persistence in WWTP (% removed) [Ready biodegradation,....] Not applicable; inorganic substance

atm-m 3 /mol = atmosphere cubic meter per mole; o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury.



## 1.4 Use/Usage Description

1.4.1 Summary of Registered Uses

Lithium hypochlorite is registered for use as sanitizer/algaecide in swimming pools and as a sanitizer for spas/hot tubs. Ther e are 18 end use products and they all contain 29 percent lithium hypochlorite (35 percent available chlorine). A listing of the registered uses of lithium hypochlorite is included in Table 5.

Table 5 – Summary of Lithium Hypochlorite Registered Uses

Use Application Method Product Application Rate Lithium Hypochlorite Application Rate (ppm) Available Chlorine Application Rate (ppm) Swimming Pool Shock Treatment Open Pour 16 ounces/6000 gallons 5.8 7.0 A

Swimming Pool Maintenance Treatment Open Pour 3.7 ounces/6000 gallons 1.16 1.4

Spa Shock Treatment Open Pour 1.0 ounce/250 gallons 8.8 10 B Spa Superchlorination Treatment Open Pour 0.5 ounce/250 gallons 4.4 5.3 B

Spa Maintenance Treatment Open Pour 0.25 ounce/250 gallons 2.2 2.7
A. Applications are made at least 12 hours prior to pool use. Rentry to the pool is not allowed until the chlorine level is below 3.0 ppm B. Labels include statements such as “Do not enter spa until available chlorine residual falls to 3.0 or below.”Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 9 of 31 

## 1.5 Regulatory History
The first product containing lithium hypochlorite as an active ingredient was registered in 1963, and it has been used chiefly as a sanitizer in swimming pools. There ar e currently 18 end use products with lithium hypochlorite as an active ingr edient. The agency completed a Reregistration Eligibility Decision (RED) for lithium hypochlorite in 1993. There are currently no outstanding Data Call-In (DCI) requirement s for this active ingredient.



### 1.5.1 Recent/Pending Regulatory Actions There are no pending regulatory actions for lithium hypochlorite.



### 1.5.2 Tolerance Information There are no tolerances or exemptions from to lerances for lithium hypochl orite because there are no currently registered uses fo r this active ingredient asso ciated with food or feed.



## 1.6 Incidents

1.6.1 Human Health

There are a total of seven incidents listed in the OPP Incident Data System for the period 9/2001 to the present (search conducted on 1/17/2014). Four of these incidents involved product misuse, such as over application of the product, use of th e product with other chlori ne sources, addition of the product to a bucket of water or use of the pr oduct on an unregistered site. One incident involved a fire in a warehouse where products were stored and another in cident involved workers at a formulation facility who e xperienced respiratory irritation.

There is one incident that occurred in 2005 where a swimmer allegedl y experienced dermal irritation effects (hives, welts and pruritus) af ter swimming in a public pool treated with the product. The pool had been treat ed approximately one hour before the swimmer was exposed.



### 1.6.2 Ecological There are no fish or wildlife poisoning incidents in OPP’s Incident Data System involving lithium hypochlorite as of January 22, 2014.


## 2 Anticipated Data Needs

The agency does not anticipate n eeding to call in any data to support this registration review.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 10 of 31 

## 3 Human Health Risk Assessment

EPA does not anticipate the need to revise the existing toxicologi cal endpoints as part of this registration review. The toxicological data base on lithium hypochlorite is adequate and will support this registra tion review case.



## 3.1 Existing Toxicological Endpoints
The primary toxicological consideration is the e ffect from exposure to the lithium ion that is produced from the reaction of lithium hypochlorite with water that produces hypochlorous acid and lithium ions. Hypochlorous acid (which is an oxidizing agent and the chemical species showing actual pesticidal activity) acts by oxidizing organic and inorganic chemical contaminants. As hypochlorous acid exerts its oxidizing effect, the chlorine reduces to chloride ions. Thus the end-products of lithium hypoc hlorite are chloride and lithium ions, both ubiquitous in the environment, and adverse e ffects from the incremental lithium hypochlorite contribution are not expected. Therefore this chemical will be evaluated qualitatively and toxicological endpoints will not be set. 1

The average background level of lithium in huma n serum has been reported as 0.014 mg/L which comes primarily from the natural content of lithium in food and drinking water (MRID 41367401). It has been estimated that the natural sources of lithium provide 2.3-4.9 mg/day of lithium. Lithium carbonate has been used as a human drug since about 1970. The intake levels are 179 to 282 mg/day of lithium ion and they provide about 4.16 to 8.33 mg/L of lithium in the serum (MRID 41367401). For the therap eutic use, the reported maximum no-toxicity levels are 10.41 to 13.88 mg/L in serum. These levels are fa r higher than the backgr ound levels and higher than any expected from pesticide use of lithium hypochlorite (MRID 41367401). In addition, lithium orotate and lithium aspartate salts are sold as over-the-counter mineral supplements that provide about 5 mg of lithium per daily dose. Clinical and epidemiologic studies on human use of lithium-containing drugs, including chronic use, have not shown any reason for concern over continued human exposure to lithium at the low leve ls of exposure expected during the pesticidal use scenario (MRID 41367401). The EPA Hazar d and Science Policy Council (HASPOC) assessed the need for acute neurotoxicity, su bchronic neurotoxicity, immunotoxicity, chronic toxicity, carcinogenicity, and reproduction and fertili ty studies on December 12 th , 2013 (TXR# 0056855). Based on a weight of evidence approach considering all the available hazard and exposure information for lithium hypochlorite, the HASPOC concluded that the acute/subchronic neurotoxicity, immunotoxicity, chronic/cancer , subchronic inhalati on, and reproduction and fertility are not required.

Past lithium hypochlorite risk assessments have relied in pa rt on the following two human studies which may have involved intentional exposu re to lithium hypochlorit e. In the course of registration review, EPA will reconsider these studies, as well as any other research involving intentional exposure of human s ubjects to lithium hypoc hlorite brought to its attention. If EPA

1 U.S. EPA 2012. Registration Review Final Work Plan: Na & Ca Hypochlorite. Docket Number EPA –HQ-OPP

2012-0004.Available at: http://www.regulations.gov /#!documentDetail;D=EPA-HQ-OPP-2012-0004-0006.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 11 of 31 decides to rely on any of these studies, EPA will ensure that all applicable regulatory requirements are met, including but not limited to the requirements for EPA ethics review and Human Studies Review Board revi ew of certain research involv ing intentional exposure of human subjects.


## 3.2 Dietary Exposure
There are no registered uses for lithium hypochl orite associated with food or feed, thus the registered uses of lithium hypochlorite are not anticipated to result in food exposures. In addition, there are no toxicological endpoints fo r lithium and thus dietary exposures from drinking water do not need to be assessed for registration review.


## 3.3 Occupational and Re sidential Exposures
Because there are no toxicological endpoints for lithium, occupational and residential exposures do not need to be assesse d for registration review.


## 3.4 Aggregate and Cumulative Exposure
Because there are no toxicological endpoints for lithium, aggregate and cumulative exposures do not need to be assessed for registration review.


## 4 Environmental Risk Assessment

An ecological risk assessment for industrial di scharge from food-proces sing plants and eating establishments was conducted for the RED (EPA , 1993). Using a screening model that assumed no environmental degradation, level of concerns we re exceeded for fish and aquatic invertebrates for a high-exposure scenario. Those uses are no t currently registered. Swimming pool use was not assessed for the RED, because no model was available to estimate the estimated environmental concerns in discharge water when pools are drained. The ecological risk assessment planned during registration review will allow the agency to determine potential acute and chronic risks to aquatic organisms expos ed to lithium hypochlorite transported from antimicrobial use sites into the aquatic environment.
The Agency has not previously conducted a risk assessment that supports a complete endangered species determination for lithium hypochlorite. Th e risk assessment will allow the agency to determine whether use of lithium hypochlorite has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designa ted critical habitats. When an assessment concludes that a pesticide’s use 'may a ffect' a listed species or its designated critical habitat, the agency will consult with the U.S. Fi sh and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.



## 4.1 Environmental Fate a nd Exposure Pathways
Lithium hypochlorite belongs to the hypochlor ite class of compounds including sodium, potassium and calcium hypochlorites. These hypochl orites rapidly dissociate in water to form hypochlorous acid (HOCl), which acts as th e active in disinfection scenarios.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 12 of 31 The agency has not conducted any environmental and transport exposure assessments for lithium hypochlorite. Lithium is a naturally occurring element and is ofte n used in industrial settings Lithium chemistry is similar to group cations li ke sodium, potassium and calcium ions. All salts of these metals are highly water soluble. 2

The agency anticipates needing to estimate surface water concentrations of Li ions from release from swimming pools and spas.



### 4.1.1 Water Quality Lithium hypochlorite is not identif ied as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Wa ter Act, based on information provided at the agency’s National Pesticides Cause of Impairme nt of Waters website (searched February 6, 2014). 3 In addition, no Total Maximum Daily Load s (TMDL) have been developed for lithium hypochlorite, based on information provided at th e agency’s National Pesticide TMDL website (searched February 6, 2014). 4 Lithium ions are not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of th e Clean Water Act, based on information provided at the agency’s National Pes ticides Cause of Impairme nt of Waters website (February 6, 2014).

3 5 There are 175 TMDL/ impaired water bodies (OW’s list 303(d)) listed for total residual chlorine (TRC) on a national level recorded be tween 2000-2007. TRC is defined as the “amount of remaining chlorine remaini ng after contact time and is equal to available residual chlorine + free availa ble chlorine.” More information on impaired water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/.



## 4.2 Ecological Effects Assessment

4.2.1 Mode of Action In the aquatic environment, toxic action is largel y due to hypochlorous acid formed when lithium hypochlorite reacts with water. Adverse eff ects of hypochlorous acid are due mainly to its corrosive action. Acute necrosis may occur. Fish gills-structure may be damaged; gill necrosis can lead to respiratory problems and asphyxiation. The protective slime coating on fish also may be removed due to corrosive acti on (EPA 1985, Singleton and Bio 1989).



### 4.2.2 Measures of Effect (Ecoto xicology Assessment Endpoints)

4.2.2.1 Submitted Data Ecological effects data are used as measures of direct and indirect effects to aquatic and terrestrial organisms. Acute and chronic toxi city data from registrant-submitted studies conducted in accordance with the 850 OCSSP Harmoni zed Test Guidelines (see Table 6) will be

2 F.A. Cotton & G. Wilkinson (Advanced Inorganic Chemistry, 7 th edition; chapter 4 and 5).

3 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

4 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 13 of 31 used to evaluate the potential di rect and indirect e ffects of lithium hypochlorite to animals and plants. Additionally, as described below, relevant data from the EPA’s Office of Water and from the open literature also may be used to evalua te potential direct and indirect effects.

All available ecotoxicity endpoints from studi es submitted by registrants are tabulated and referenced in the Ecological Effects Profile (App endix C). OPP uses the most sensitive of these endpoints for assessing acute and chronic risks to each aquatic receptor group. The avian toxicity endpoint is used to determine the need for precautionary labeling for hazards to wildlife. The Agency has a complete database to determ ine the effects of hypochl orous acid on aquatic organisms. The endpoints selected for the asse ssment for hypochlorous acid from the data submitted to the agency are provided in Table 6.

Table 6 – Available Ecological Effects Endpoin ts for the Ecological Assessment of Lithium Hypochlorite

Receptor Group Test Material Risk Scenario Toxicity Endpoint (TRC or CPO) a Reference

Freshwater fish TGAI Acute LC50 = 200 μg ai/L 00094672
Chronic -- None

Freshwater invertebrates TGAI Acute EC50 = 230 μg ai/L 00094674
Chronic -- None

Estuarine/marine fish TGAI Acute -- None
Chronic -- None

Estuarine/marine

invertebrates TGAI Acute -- None

Chronic -- None
Sediment-dwelling invertebrates TGAI Acute and Chronic -- None

Algae TGAI EC 50 NOAEC -- None

Aquatic vascular Plants TGAI EC 50 NOAEC -- None

Birds TGAI Acute LD50 = mg ai/kg 00094673

a Toxicity values are expressed as total residual chlorine (TRC) for freshwater organi sms and as chlorine-produced oxidants (CPO) for seawater organisms (EPA 1985).

4.2.2.2 Office of Water Data

EPA’s Office of Water’s Ambient Water Quality Criteria for Chlorine

4 6 provides additional data that will be used in the risk assessment. Th e document contains a review of open literature on acute and chronic effects of chlo rine. Based on the available toxi cological endpoints, freshwater and saltwater organism acute and chronic wate r quality criteria (expressed as total residual

6 See EPA’s Office of Water’s Ambient Water Quality Criteria for Chlorine -1984 (EPA, 1985) at: http://water.epa.gov/scitech/swguidance/standards/uplo ad/2001_10_12_criteria_ambientwqc_chlorine1984.pdfDocket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 14 of 31 chlorine (TRC) for freshwater and chlorine-pro duced oxidants (CPO) for seawater) are derived. The current values are as follows:

 Freshwater Criterion Maximu m Concentration = 19 μg/L;

 Freshwater Criterion Continuous Concentration = 11 μg/L;

 Saltwater Criterion Maximum Concentration = 13 μg/L; and

 Saltwater Criterion Continuous Concentration = 7.5 μg/L

4.2.2.3 Open Literature The agency is aware of reviews of ecotoxicity data for lithium which will be obtained from the open literature for the risk assessment of lithium ions and salts. No data have been submitted to determine the toxicity of the lithium ion; theref ore, the open literature will be evaluated to determine the potential for its toxicity when the risk assessment is conducted.

Open literature studies also will be obtained via EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched when th e risk assessment is prepared. Any acute or chronic endpoints more sensitive than what is currently available will be used in the risk assessment and risk characterization. Any relevant ecotoxicity data on the lithium ion also will be used. The Evaluation Guidelines for Ecological To xicity Data in the Open Literature are discussed in more detail on the agency’s website at www.epa.gov/pesticides/science /efed/policy_guidance/team_author s/endangered_species_reregi stration_workgroup/esa_evalua tion_open_literature.htm.



## 4.3 Exposure Analysis Plan

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates The agency is currently developing an assessmen t method to provide estimates of exposure for pesticides applied to swimming pools and potenti ally released into the environment when pools are drained. The agency anticipat es using all available information when the risk assessment is conducted for lithium hypochlorite.


## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its 1993 reregi stration decision for lithium hypochlorite, EPA reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p),Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 15 of 31 lithium hypochlorite is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the agency must scr een all pesticide chemi cals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013

5 7 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening batt ery, please visit our website. 8

6 

## 6 Optional Label Changes

The agency invites comment on any label amendmen ts that could be considered to reduce the possibility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions, and/or improve label clarity.


## 7 Guidance for Commenters

7.1 Preliminary Work Plan
The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the lithium hypochlorite registration review

case.

7 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of chemicals.

8 http://www.epa.gov/endo/Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 16 of 31 

### 7.1.1 Trade Irritants Through the registration review process, the ag ency intends to solic it information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. The agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specifici ty as possible regarding the nature of the

concern.



### 7.1.2 Water Quality The agency invites submission of wate r quality data for this pesticide

. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Im paired Water Body and Other Water Quality Data in OPP’s Registration Review Risk A ssessment and Management Process

7 9 in order to ensure they can be used quantitatively or qualitativel y in pesticide risk assessments.



### 7.1.3 Environmental Justice

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to lithium hypochlorite compared to the general population. Please comment if you are aware of any sub-populations that may have atypical, unusually high exposure compared to th e general population.



### 7.1.4 Structure Activity Relationships EPA must rely upon information of appropriate qu ality and reliability for each decision made by the agency. In the Office of Pesticide Program s (OPP), the evaluation process for a pesticide chemical traditionally begins with the applicant’ s submission of a set of studies conducted with the specific pesticide chemical of interest. The us e of the results of such testing (measured data) is a logical, scientifically rigorous proce ss that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant interest in alternat ive techniques, i.e., tech niques other than data generation that could significantly inform the agency’s decision-making process. Recently, OPP has made increasing use of stru cture activity relationship (SAR ) as part of its regulatory decision-making process. In the SAR process, a ch emical's molecular structure is compared to that of other chemicals for which data are availabl e. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biol ogical properties are a f unction of (or directly

9 http://www.epa.gov/oppsrrd1/regist ration_review/water_quality_sop.htmDocket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 17 of 31 related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured da ta on a single physical, chemical, or biological property is used to derive a model (an equatio n) to predict the valu e of that property.

Since SAR assessments and QSAR modeling are anothe r set of tools that are available to Agency scientists, OPP has begun a proce ss shift that envisions shifting from the current study-by-study approach to an approach in which the use of pr edicted data, generated us ing validated models, is considered along with information from open litera ture and studies specifically generated under Part 161 requirements. All relevant information w ould be considered as pa rt of a weight-of-theevidence evaluation.

At this time, EPA believes that for certain e ndpoints, especially physi cal/chemical and fate properties, that SAR and QSAR might be effect ively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological prope rties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a screening-level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.

If stakeholders believe that submission of predic ted data can fulfill one of the data needs for the lithium hypochlorite case, then the agency invites submission of this information. The submitter would be expected to supply a ra tionale describing the utility of the information and provide documentation on the scientific va lidity of the information. The de termination that the predicted data fulfills the data requirement would be at the sole discretion of the agency. Pre-submission consultation with the agency is encouraged.



### 7.1.5 Additional Information

Stakeholders are also specifically asked to provid e available information a nd data that will assist the agency in refining its risk assessments, including any species-spec ific ecological effects determinations. The agency is interested in receiving the following information:

1. Confirmation on the following label information: A. Sites of application B. Formulations C. Application methods and equipment D. Maximum application rates E. Frequency of application, applicatio n intervals and maximum number of applications F. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non-agricultura l uses (e.g., material s preservation) 5. Typical application interval 6. State or local use restrictionsDocket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 18 of 31 7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the agency 8. Monitoring data



## 8 Next Steps

After the 60-day comment period closes in May 2014, the agency will review and respond to any comments received in a timely manner, and then issue a Final Work Plan for the lithium hypochlorite case.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 19 of 31 

## 9 References

00037615 Nelli, J. R. The Build-up of Lithiu m Ion in Swimming Pool Waters and Its Effect on Swimmers. (1964) Unpublishe d study submitted by Lithium Corp of America.

00234351 a. Acute Oral Toxicity Study in 

### Rats. (1977) Unpublishe d study prepared by Hazleton and submitted by Lithium Cor p. of America. St udy No. 668-103. b. Acute Dermal Toxicity Study in Rabbits. (1977) Unpublished study prepared by Hazleton and submitted by Lithium Corp. of America. Study No. 668-104.

c. Primacy 

### Skin Irritation Study in Rabbits. (1977) Unpublished study prepared by Hazleton and submitted by Lithium Corp. of America. Study No. 668-105. d. Acute Eye Irritation Potential Study in Rabbits. (1977) Unpublished study prepared by Hazleton and submitted by Lithium Corp. of America. Study No. 668-106.

00252294 Guinea Pig Maximization Test with Lithcoa Lithium Hy pochlorite (1984) Unpublished study prepared by Hazleton. Study No. 668/115.

40545701 Yang, L. (1988) CHO/HGPRT Mutation Assay: 11945 Lithium Hypochlorite Study No. T5674.332005. Unpublished study prepared by Microbiological Associates Inc. 30 p.

40545702 Batt, K. (1987) Salmonella/Ma mmalian-Microsome Plate Incorporation Mutagenicity Assay (Ames Test): Study No. 187-0975. Unpublished study prepared by FMC Corp., Gene tic Toxicology Laboratory. 33 p.

40545703 Putman, D. (1988) Chromosome Ab errations in Chinese Hamster Ovary (CHO) Cells: 11945 Lithium Hypoch lorite I : Study No. T5674. 337020. Unpublished study prepared by Microbi ological Associates, Inc. 29 p.

40545704 Curren, R. (1988) Unscheduled DNA Synthesis in Rat Primary Hepatocytes:11945 Lithium Hypochlor ite I :Final Report: T5674.380017. Unpublished study prepared by Microbi ological Associates, Inc. 28 p.

40648101 Lochry, E. (1988) Developmental T oxicity (Embro/Fetal Toxicity and Teratogenic Potential) Study of Lithium Hypochlorite Administered Orally via Gavage to Crl:CD(SD)BR Presumed Pr egnant Rats: Spon sor's Study No.187- 0978. Unpublished study prep ared by Argus Research Laboratories, Inc. 236p.

40746701 McCarty, J.; Carter, S.; Fletcher, M.; et al. (1988) Study of Lithium Absorption by Users of Spas Treated with Lithium Ion: Study No. 187-0981. Unpublished study prepared by FMC Toxicology Dept. 225 p.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 20 of 31 

### 40803901 Freeman, C. (1988) Lithiu m Hypochlorite: Acute Oral Toxicity Study in Rats: Study No. 187-0982. Unpublished st udy prepared by FMC Toxicology Laboratory. 47 p.

41367401 Todhunter, J.; Mandava, N. (1990) S upplemental Data and Documentation in Support of Data Waiver Requests file d by Lithium Corpor ation of America dated November 24, 19 89: FMC Study No. I90-1108. Unpublished study prepared by SRS International. 1424 p.

44643001 Signorin, J. (1998) Lithium hypoc hlorite commercial: Acute inhalation toxicity study in rats: Study No. 198 -225. Unpublished study prepared by FMC Toxicology Laboratory. 70p.

7257 Lithium Corporation of America (1969) Analysis of Lithium hypochlorite. Includes R & D method no. 210 dated Nov 1969. (Unpublishe d study received Dec 29, 1972 under 7675- 1; CDL: 008072-A)

7258 Lithium Corporation of Ameri ca Product Information: LCA Lithium hypochlorite: Data Sheet 111-463. (Unpub lished study received Aug 28, 1964 under 7675-2; CDL:008073-A)

94669 Lithium Corporation of American (1977) Storage Stability Data for Lithcoa Lithium Hypochlorite. (Unpublished study received Aug 24, 1979 under 7675- 4; CDL:246731-B)

93138001 Cinq-Mars, R. (1990) L ithium Corporation of Amer ica Phase 3 Summary of MRID 00051222 and Relate d MRIDs 0000725 8, 00031511, 00094670, 00007261, 00094669, 00094670. Chemical and Physi cal Properties of Lithium Hypochlorite. 34 p.

42940801 Hatch, H. (1993) Beginning Materi als and Manufacturing Process: FIFRA Reregistration of Lithium H ypochlorite: Product Class- C: Data Gaps in Phase III Submission. Unpublished study. 18 p.

42967001 Hatch, H. (1993) FIFRA Reregistra tion of Lithium Hypochlorite, Product Class-C: (Response to) Data Gaps in Phase III Submission: Solubility. Unpublished study prepared by FMC Corp. 7 p.

42967002 Hatch, H. (1993) FIFRA Reregistra tion of Lithium Hypochlorite, Product Class-C: (Response to) Data Gaps in Phase III Submission: Vapor Pressure. Unpublished study prepared by FMC Corp. 4 p.

42967003 Hatch, H. (1993) FIFRA Reregistra tion of Lithium Hypochlorite, Product Class-C: (Response to) Data Gaps in Phase III Submission: Dissociation Constant. Unpublished study prepared by FMC Corp. 10 p.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 21 of 31 

### 42991801 Eschbach, J. (1993) Me thod Validation and Determin ation of Lithco Lithium Hypochlorite for Swimming Pool/Spa Sa nitation and Algea (sic) Control. Final Report: Lab Project Number : 93/9078: P93/0035. Unpublished study prepared by Pharmaco-LSR. 55 p.

EPA. 1985. Ambient Water Quality Crit eria for Chlorine - 1984. Regulations and Standards, Criteria and Standards Division, Office of Water, Washington, DC.

Singleton, H.J. and R.P. Bio. 1989. Ambien t Water Quality Crite ria for Chlorine Technical Appendix. Resource Quality Section, Water Management Branch, Ministry of Environment, province of British Columbia, Victoria, B.C.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 22 of 31 

# Appendix A Toxicology Profile

Acute Toxicity for Product Labeling

As summarized in Table 1, in acute toxicity stud ies, lithium hypochlorite has been shown to have data from an acute oral toxici ty study in rats indicated LD 50 of 748 mg/kg for males and 555 mg/kg for females. This study, which used techni cal lithium hypochlorite, indicates category III toxicity (MRID 40803901). A second acute oral toxicity study (M RID 234351) in rats that was conducted only in male animals is useful for i ndicating the nature of the observed effects. The effects in the rats were primarily due to the corrosive nature of the substance and included inflamed gastric mucosa and lungs, distende d stomach, congested kidneys, yellow purulent material in chest cavity, and la bored respiration. The oral LD 50 for males in this study was 286 mg/kg. The dermal LD 50 was approximately 8100 mg/kg for fe male and male rabbits, which is category IV toxicity (M RID 234351). The inhalation LC 50 was 1.8 mg/L for males, 2.1 mg/L for females, which combines to 2.0 mg/L LC 50 , which indicates category III toxicity (MRID 44643001). The effects were dermal necrosis, severe erythema, anorexia, depression, and lack of body fat. The corrosive nature of lithium hypochlor ite puts this compound in toxicity category I for both eye irritation and dermal irritation. A dermal sensitization study, which used solid lithium hypochlorite as a 10% solution in saline, did not demonstrate any dermal sensitization (MRID 252294).

Table 7 – Acute Toxicity Data for Lithium Hypochlorite

Guideline No. Data Requirement/ Species Conclusions/Acceptable/ Comments Tox Cat MRID

870.1100 Acute oral toxicity - Rat 746 mg/kg males 555 mg/kg females III 40803901

870.1200 Acute dermal toxicity - Rabbit 8100 mg/kg both sex IV 234351

870.1300 Acute inhalation toxicity 1.8 mg/L males 2.1 mg/L females 2.0 mg/L combined III 44643001

870.2400 Acute eye irritation - Rabbit Severe irritation I 234351

870.2500 Acute dermal irritation – Rabbit Severe irritation I 234351

870.2600 Skin sensitization – Guinea pig Not sensitizing N.A. 252294Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 23 of 31 

## Subchronic Toxicity

Subchronic inhalation studies we re waived by the HASPOC (TXR # 0056855). As indicated by study MRID 40746701, there is no significant absorption of lithium through th e intact skin and thus no long term dermal exposure risk. Subchroni c oral studies are not co nsidered required as all oral exposure is considered belo w normal ingestion via food and water. 

## Developmental Toxicity

In a developmental toxicity study four groups of 25 female rats were given, by gavage, lithium hypochlorite on gestation days six through fift een (MRID 40648101) with one additional group of 25 rats as control. The dose levels we re 0, 10, 50, 100, or 500 mg/kg/day using 30% test substance in water. The maternal and deve lopmental NOELs were 100 mg/kg/day of lithium hypochlorite, which is equivalent to 4.1 mg/kg/ day of lithium. The maternal LOBL was at 500 mg/kg/day, based on deaths, redu ced weight gain, reduced food consumption, and inflamed and congested respiratory system. The developmen tal LOEL was also at 500 mg/kg/day, where the fetuses showed reduced fetal weight, dilated renal pelvis, bifid vertebrae, wavy ribs, and unossified foot bones. A survey of animal st udies in the published literature (MRID 41367401) generally found the no-effect levels at or above 4.5 mg/kg/day of lithium. None of the studies showed developmental effects at levels belo w those which showed maternal toxicity. 

## Reproductive Toxicity

These studies were waived by the HASPOC (TXR # 0056855). 

## Chronic Toxicity and Carcinogenicity

These studies were waived by the HASPOC (TXR # 0056855). 

## Mutagenicity

Technical lithium hypochlorite was negative, with and without metabolic activation, in an Ames test for mutagenicity using five strains of Salmonella (MRID 40545702). A study of unscheduled DNA synthesis in rat hepatocytes using technical lithium hypochlorite was also negative (MRID 40545704). Lithium hypochlorite was negative in the CHO/HGPRT mutation assay with and without activation (MRID 40545701). A test for ch romosome aberration in CHO cells with technical lithium hypochlorite was positive (MRI D 40545703). However, a test for chromosomal aberrations in rat bone marrow cells was ne gative with lithium hypochlorite (MRID 40907500).


## Metabolism

The lithium ion is rapidly absorbed after ingestion and is distributed through the body. It is excreted by the kidney and most of the ion is excreted within 6-8 hour s after ingestion (MRID 00037615). 

## Other Toxicological Effects

The immunotoxicity study was wa ived by the HASPOC (TXR # 0056855).Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 24 of 31 

# Appendix B Environmental Fate and Transport of Lithium Hypochlorite

For inorganic-like hypochlorites, it is important to understand the speciation of these actives in the environmental medium like water to be able to determine risk concerns . All other parameters remaining constant (temperature, redox potential etc.), the pH ch anges vs. the speciation process becomes a very important fate fact or for hypochlorite as seen below.

pH profile of hypochlorite:

It has been estimated the changes due to protol ysis (hydrolysis) of a solution containing OCl

- can be represented by the pH profile. The numeri cal data on the percent of HClO and ClO

- from pH 4 to 11 as shown below:

pH 4 100% HClO pH 6.3 95% HClO/ 5% ClO pH 7.2 70% HClO / 30% ClO pH 7.7 50% HClO/ 50% ClO pH 8.0 21% HClO/ 79% ClO pH 11 100% ClO

The data above indicates that it is the OCl

- and HOCl moieties that are the actives in the alkali hypochlorite (Na, K, Ca, and Li) systems under environmental conditions between pH 4 and 11. However, under different pH condition other moieti es are present as indi cated in the diagrams shown below. 10

8 Versatility of chlorine and oxygen reactions:

Chlorine is one the most versatile elements, part icularly in regards to its reaction with oxygen. Chlorine shows numerous oxidation states (state s of reactivity, from + 7 to -1). The following diagrams illustrate a number of facts: a) from the highest oxidation state in ClO 4 - of + 7 to -1 in Cl

- the reduction potentials are such that the reactions take place s pontaneously in acidic or basic aquatic medium; b) The reve rse reactions such as Cl - to ClO 4 - are not spontaneous.

8 10 U.S. EPA 2012. Registration Review Final Work Plan: Na & Ca Hypochlorite. Docket Number EPA –HQ-OPP2012-0004.Available at: http://www.regulations.gov /#!documentDetail;D=EPA-HQ-OPP-2012-0004-0006.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 25 of 31 Under acidic conditions:



### ClO 4 - 

###  ClO 3 - 

###  ClO 2 - 

###  HClO 2 

###  HOCl  Cl 2 

###  Cl

-

1 2 3 4 5 6 7

Where:

1 = perchlorate ion; 2= chlorate ion; 3= chlo rite ion; 4= chlorous acid; 5= hypochlorous acid 6= chlorine; 7= chloride ion Note : the oxidation state of chlorine in 1 = +7 and oxidation state in 7 = -1

Under basic conditions:



### ClO 4 - 

###  ClO 3 - 

###  ClO 2 

###  ClO 2 - 

###  OCl

- 

###  Cl 2 

###  Cl

-

1 2 3’ 4 5’ 6 7

Where 3’= chlorine dioxid e and 5’ = hypochlorous ion

It is not expected that hypochlorite will convert into highly oxidized species under the present use conditions. Thus depending on the pH, and oxidizing and reducing conditions in the environmental media, hypochlorite goes through speciation. 11

9 Lithium element belongs to the alkali group of me tals in the periodic table. Lithium is the smallest atom in the group and forms the smallest cation (Li + ) after hydrogen ion. The aquatic chemistry of lithium salts is similar to sodium an d potassium salt: chlorides, oxides, hydroxides, carbonates, and hypochlorites are hi ghly soluble in water. Lithium reacts with organics to form organolithum substances. It is present in soil s and sediments as a background mineral not as complexes but as salts. 12

10 In its Hazard Substance Database (HSDB), T OXNET has listed an Environmental Fate/Exposure Assessment.

11 13 It is summarized here: Lithium is present in earth’s crust at an es timated level of 20-70 ppm by wt. It is widely distributed in the natural environmental media like minerals, rocks, soils, and natural waters and in many mineral springs. It sorbs to humic acids with a K oc 14

12 of about 4.6, which makes it mobile from humic acid surfaces. Because of its many uses, including the present use as a sanitizer in swimming pools and spas, lithium is released to the environment through many waste streams. It is non-volatile and is likely to exist in particulate forms in these matrices. In aquatic medium, it absorbs to the suspended so ils and sediment (measured K f 14 values ranged 4.5 to 5.5, which

9 11 U.S. EPA 2012. Registration Review Final Work Plan: Na & Ca Hypochlorite. Docket Number EPA –HQ-OPP2012-0004.Available at: http://www.regulations.gov /#!documentDetail;D=EPA-HQ-OPP-2012-0004-0006.

10 12 F.A. Cotton & G. Wilkinson (Advanced Inorganic Chemistry, 7 th edition; chapter 4 and 5).

13 http:/pubchem.ncbi.nih.gov/toc/summary_toc.cgi?tocid=351&sid=96024823

5 55 14 Kf is the Freundlich adsorption coefficient for whole sediment. Koc is the Kf/% organic carbonDocket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 26 of 31 makes it loosely bound to such surfaces. Essentially lithium ions will be partitioned from soils and sediments to aqueous medium. Other possible pathways for lithium ion to be part of such environmental media are: to precipitate, or go through ligand exchange (e.g. sodium substitution for lithium). It is not likely to bioconcentrate as it is an ion. A few studies conducted on ground water on 118 sites in Western San Joaquin Valley, CA lithium concentrations was measured between 50 to 190 μg/l, during spring period; in Connecticut , the lithium was detected in 31/83 sample wells, with a median lithium concentration of < 4.0 μg/L.

Measurements of lithium were taken in various US lakes, and waterways like Great Lakes basin, Lake Superior and Lake Michigan, Lake Erie/ green river, and the amounts varied depending on the anthropogenic use levels in these areas.

A number of studies were conducte d to estimate lithium ion concentration in drinking water . In 94 large cities of US, the drinking water contai ned an average of 1.9 μg/L of lithium. In A Venezuelan Andes, the amounts were in the range of 5 to 80 μg/L.

Lithium is found in onions, grapefruit in Texas, Ca lifornia, etc.; in orange from Florida. Lithium has been detected in leguminous plants. Lithium has been detected in various aquatic organisms like, cod, and mussels.

There are no current federal standards for lithium in drinking water; average lithium intake is 2 mg/day.

13 15

15 https://www.vdh .virginia.gov/Epidemiol ogy/DEE/.../pdf/lithium.pdfDocket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 27 of 31 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Organisms

Birds

An acceptable acute-oral (LD50) study categorizes li thium chlorite as being moderately toxic to birds. The guideline for an acute-oral test ( 850.2100) is satisfied. Diet ary studies (850.2200) are not required. However, four dietary studies have been submitted and indicate that lithium chlorite is practically nontoxic to birds when admi nistered in the diet. No additional data avian toxicity data are anticip ated to be needed.

Avian Acute-oral and Dietary Toxicity

Test Species Test Material (% ai) Toxicity Toxicity Category EPA Study ID

Mallard ( Anas platyrhynchos ) 29 LD50 = 567 mg ai/kg bw Moderately toxic 00094673 Acceptable

29 LC50 >5000 ppm Practically nontoxic 00104674 Acceptable

15 LC50 >10,000 ppm Practically nontoxic 00104674 Supplemental

Northern bobwhite ( Colinus virginianus ) 29 LC50 >5000 ppm Practically nontoxic 00104674 Acceptable

15 LC50 >10,000 ppm Practically nontoxic 00104674 Supplemental

Nontarget Insects

Toxicity data for beneficial insects (850.3020, 850.3030) are not anti cipated to be required for the use patterns of lithium hypochlorite

, because lithium hypochlorite is not registered as a wood preservative.


### Toxicity to Aquatic Organisms

Freshwater Fish

The available acute toxicity st udies categorize lithium hypochlor ite as being moderately to highly toxic to freshwater fish. The guideline (850.1075) for acute t oxicity testing is satisfied. No chronic data (fish early-lif e stage, 850.1400) are available. However, the need for chronic toxicity data can be fulfille d from EPA’s Office of Water’s Ambient Water Quality Criteria for Chlorine - 1984 (EPA 1985). No additional fish toxicity data are anticipated to be needed.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 28 of 31 Acute Toxicity to Freshwater Fish

Test Species Test Material (% ai) Toxicity Endpoint (μg ai/L) Toxicity Category EPA Study ID

Rainbow Trout ( Oncorhynchus mykiss) 29 96-hr LC50 = 200 Highly toxic 00094672 Acceptable
15 96-hr LC50 = 2500 Moderately toxic 00007302 Supplemental Bluegill ( Lepomis macrochirus ) 29 96-hr LC50 = 280 Highly toxic 00094672 Acceptable

15 96-hr LC50 = 6170 Moderately toxic 00007302 Supplemental

Freshwater Invertebrates

The acute toxicity study for the waterflea categor izes lithium hypochlorite as being very highly toxic to freshwater invertebrates. The guideline (850.1010) for acute toxicity testing is satisfied. No chronic data (life-cycle, 850.130 0) are available. However, the need for chronic toxicity data can be fulfilled from EPA’s Office of Water’s Ambient Water Quality Criteria for Chlorine - 1984 (EPA 1985). No additional aquatic i nvertebrate toxicity data are anticip ated to be needed.

Toxicity to Freshwater Invertebrates

Test Species Test Material (% ai) Toxicity Endpoint (μg ai/L) Toxicity Category EPA Study ID

Waterflea ( Daphnia magna ) 29 48-hr EC50 = 230 Very highly toxic 00094674 Acceptable

Estuarine/Marine Fish and Invertebrates

No acute or chronic data are available. Acute to xicity studies needed for the TGAI include tests for a fish sp. (850.1075), a bivalve sp. (850.1025 or 850.1055), and one additional invertebrate sp. (850.1035); to address these ne eds, the agency anticipates us ing the available data from EPA’s Office of Water’s Ambient Water Quality Crite ria for Chlorine - 1984 (EPA 1985).

Aquatic Plants

No data are available. Studies needed for the TGAI include a toxicity test with a vascular species (850.4400), toxicity tests (850.4500) with 3 algal species (green algae, freshwater diatom, marine diatom), and a toxicity test using cya nobacteria (850.4550); to address these needs, the agency anticipates using the available da ta from EPA’s Office of Water’s Ambient Water Quality Criteria for Chlorine - 1984 (EPA 1985).

Sediment toxicity

Based on the environmental-fate properties of lithium hypochlorite (see section 4.1), lithium hypochlorite is not anticipat ed to accumulate in sediments. Ther efore, sediment toxicity data are not anticipated to be required.Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 29 of 31 Appendix C References

94673 Piccirillo, V.J. (1977) Final Report: Acute Oral LDI50 Study in Mallard Ducks: Project No. 668-107. (Unpublished study received Apr 25, 1978 under 7675-4; prepared by Hazleton Laboratories America, Inc. and Truslow Farms, Inc., submitted by Lithium Corp. of America, Gastonia, N.C.; CDL:246732-D)

104674 Piccirillo, V.J. (1977) Final Report: Subacute Dietary LC I50 Study in Bobwhite Quail: Project No. 668-109. (Unpublished study receiv ed Apr 25, 1978 under 7675-4; prepared by Hazleton Lab- oratories America, Inc. and Truslow Farms, Inc., submitted by Lithium Corp. of America, Gastonia, N.C.; CDL:246732-B)

94672 Buccafusco, R.J. (1978) Acute Toxicity of Lithcoa Lithium Hypochlorite to Rainbow Trout ( Salmo gairdneri ): Report #BW-78- 2-031. (U npublished study received Apr 25, 1978 under 7675-4; prepared by EG & G Bionomics, submitted by Lithium Corp. of America, Gastonia, N.C.; CDL:246732-C)

7302 Sleight, B.H., III (1972) Bioassay Report: Acut e Toxicity of K-70 Algaecide to Bluegill ( Lepomis macrochirus ) and Rainbow Trout ( Salmo gairdneri ). (Unpublished study received Dec 12, 1972 under 5135-17; prepared by Bionomics, Inc., submitted by Water Services, Burbank, Calif.; CDL:132135-C)

94674 LeBlanc, G.A. (1978) Acute Toxicity of Lithcoa Lithium Hypochlorite to the Water Flea ( Daphnia magna ): Report #BW-78-2-032. (Unpublis hed study received Apr 25, 1978 under 7675-4; prepared by EG & G Bionomics, submitted by Lithium Corp. of America, Gastonia, N.C.; CDL:246732-E)Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 30 of 31 

# Appendix D Product Chemistry

Lithium hypochlorite product chemistry information is summarized in Table D1 (source: MRIDs 7257, 7258, 94669, 93138001, 42940801, 42967001, 42967002, 42967003, 42991801, 31007- 02, 31007-03, 5045001-15).

Table D1 – Product Chemistry of Lithium Hypochlorite

Guideline No. Physical and Chemical Properties Lithium hypochlorite
830.1550 Product identity and composition Refer to Table 3. 830.1600 Description of materials used to produce the product Confidential Business Information (CBI).

830.1620 Description of production process CBI. 830.1650 Description of Formulation Process CBI. 830.1670 Discussion of Formation of Impurities CBI. 830.1700 Preliminary analysis CBI. 830.1750 Certified limits CBI. 830.1800 Enforcement analytical method FMC Lithium Division method 05-LTM-564. 830.1900 Submittal of samples CBI. 830.6302 Color 830.6303 Physical St ate Granular solid. 830.6304 Odor Odorless or with slight odor of chlorine.

830.6313 Stability to normal and elevated temperature, metals/metal ions Stable and retains 90% of available chlorine when stored in fiber containers with aluminum overwrap at 75F (23.88°C) and 75% relative humidity for 4 months. 830.6314 Oxidation/Reduction Lithium hypochlor ite with 39% available chlorine has some oxidizing effect. Strong Oxidizing Agent. Oxidizer. Lithium hypochlorite is a powerful oxidizing agent,
p articularly in the presence of wate r or at higher temperature as it decomposes to release oxygen and chlorine gases. Forms highly explosive NCl 3 on contact with urea or ammonia. When heated or on contact with aci ds, it produces highly toxic fumes of chlorine gas. 830.6315 Flammability Not applicable. Noncombustible. 830.6316 Explodability Not explodable. 830.6320 Corrosion Characteristic Corrosive.

830.7000 pH 9.9 (available Cl 2 - 100 ppm) in distilled water at 25°C. 10.3 (available Cl 2 - 200 ppm) in distilled water at 25°C. 10.7 (available Cl 2 - 300 ppm) in distilled water at 25°C.

11 at 25 °C (1% Solution). 830.7050 UV/Visible Absorption Not reported. 830.7100 Viscosity Not applicable. 830.7200 Melting point 135 °C with decomposition. 830.7220 Boiling point Not applicable. 830.7300 Density 0.531 g/cm 3 (20 °C).Docket Number EPA-HQ-OPP-2013-0606 www.regulations.gov

Page 31 of 31 Guideline No. Physical and Chemical Properties Lithium hypochlorite
Bulk Density: 58 lbs/ft 3

.

830.7370 Dissociation Constant 3.2 x 10 -8 (of HOCl in aqueous solution). Lithium hypochlorite dissociates completely on dissolving in water, and is soluble to 43 grams product to 100 grams water. 830.7550 Partition coefficient ( n -octanol/water) Not applicable. 830.7840 Solubility in water 43% by weight at 25°C. 430 g/L. 830.7860 Solubility in organic solvents Product should be mixed only with water.
830.7950 Vapor pressure Not applicable. 6.63 x 10 -17 mm Hg (EPI Suite v4.1).

atm-m 3 /mol = atmosphere cubic meter per mole; o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury.